New research published in Nature Communications details the discovery of a potential new drug that selectively kills dormant cancer cells in tumors by inducing mitochondrial dysfunction.

The research team, led by Prof. Stig Linder of the Karolinska Institutet and Uppsala University, both in Sweden, says a small molecule called VLX600 has been proven effective in killing dormant colon cancer cells in a variety of in vivo and in vitro models.

The investigators explain that in solid tumors bigger than a few millimeters, a lack of both oxygen and nutrients is common as a result of insufficient blood vessel growth. They say this causes cancer cells to become dormant.

After these dormant cancer cells have received treatment, they begin to divide and tumors start to grow. The researchers explain that this process plays a part in the resistance of solid tumors to radiotherapy and chemotherapy.

However, in their new study, the research team discovered that in areas of tumors that lack oxygen and nutrition, there is also a lack of mitochondrial energy production that the cancer cells are unable to make up for.

"Our ﬁndings suggest that tumor cells in nutritionally compromised microenvironments are sensitive to disturbances of mitochondrial function, resulting in a bioenergetic catastrophe," the researchers explain.

VLX600 induces mitochondrial dysfunction

When applied to colon cancer cell lines in vitro that lacked nutrients and oxygen, the VLX600 molecule was found to induce this mitochondrial dysfunction, causing cancer cells to die.

On testing the VLX600 molecule on colon cancer cell lines in vivo, it was found to suppress tumor growth.

Furthermore, the molecule boosted the efficacy of irinotecan - a drug already used to treat patients with colon cancer.

Commenting on their discovery, the researchers say:

"Our ﬁndings suggest that tumor cells in metabolically compromised microenvironments have a limited ability to respond to decreased mitochondrial function, and suggest a strategy for targeting the quiescent populations of tumor cells for improved cancer treatment."

The investigators say they have developed the VLX600 molecule as a drug in collaboration with Vivolux AB - a biotech company based in Uppsala, Sweden.

The research team notes that they are planning to carry out a clinical study of the drug later this year alongside researchers from the US.

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